Fasting builds a favorable environment for effective gut microbiota modulation by microbiota-accessible carbohydrates.

Dietary nutrients are an important determinant of gut microbial composition (Asnicar et al, Nat Med 27:321-332, 2021; Arifuzzaman. et al, Nature 611:578-584, 2022; Bolte. et al, Gut 70:1287-1298, 2021). Commensal bacteria compete and cross-feed on host-derived nutrients to maintain stable gut microbial communities (Kolodziejczyk. et al, Nat Rev Microbiol. 17:742-753, 2019; Ma. et al, Gut Microbes 12:1785252, 2020). However, the changes to the gut bacteria induced by fasting are not well-defined. Here, we propose a powerful method to selectively and effectively increase specific gut bacteria by combining fasting and administration of microbiota-accessible carbohydrates (MACs). Fasting alters the gut microbial community structure, and the fasting + MAC intervention has profound effects on the gut microbiome with increased specific bacteria and fecal IgA levels than MAC administration alone. The changes in gut microbiota composition are specific to the type of MAC administered. We identified the most effective protocol to combine with fasting + MAC to increase the levels of specific bacteria such as Bifidobacterium. Overall, the integrating fasting with MACs effectively alters the gut microbiome, suggesting that fasting can prepare the environment for gut microbial modulation by MACs.